The high per levels in cry1,2 -/-mice and the low per levels in clock mutant mice [ 26 47 ] correlate with their contrasting sleep phenotype (see above; [ 34 ] ). In this context, the sleep abnormalities in dbp -/-mice might also be related to a reduction in per expression since, at least in vitro , DBP can amplify the CLOCK:BMAL1-induced transcription of per [ 48 ] , but it is not known whether per transcript levels are altered in dbp -/-mice.

Deletion of the cryptochromes disinhibits the transcriptional activation of CLOCK:BMAL1 and NPAS2:BMAL1 target genes, resulting in increased levels of their transcripts in the SCN, liver, and retina [ 20 23 25 ] . We assayed the expression in the brain of three genes that are known targets of cryptochrome mediated transcriptional inhibition: albumin D-binding protein ( dbp [ 26 ] ), period (per)1 , and per2 [ 20 23 27 ] , in the middle of the daily light period.

Defining effective control of BP by the criteria of either maintaining diastolic blood pressure (DBP) ≤ 95 mmHg or achieving a least ≥ 15 mmHg decrease in DBP, the authors summarized the following results: 'Eighty per cent of randomized patients completed the protocol with effective control of BP and no side effects.